RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway (Homo sapiens)

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(HMDB identifier normalization)
 
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Please access this pathway at [http://www.netpath.org/netslim/rankl_pathway.html NetSlim] database.
Please access this pathway at [http://www.netpath.org/netslim/rankl_pathway.html NetSlim] database.
If you use this pathway, you must cite following paper: Raju, R., Balakrishnan, L., Nanjappa, V., Bhattacharjee, M., Getnet, D., Muthusamy, B., Thomas, J. K., Sharma, J., Rahiman, B. A., Harsha, H. C., Shankar, S., Prasad, T. S. K., Mohan, S. S., Bader, G. D., Wani, M. R. and Pandey, A. (2011). A comprehensive manually curated reaction map of RANKL/RANK signaling pathway. Database (Oxford). 2011, bar021.</Comment>
If you use this pathway, you must cite following paper: Raju, R., Balakrishnan, L., Nanjappa, V., Bhattacharjee, M., Getnet, D., Muthusamy, B., Thomas, J. K., Sharma, J., Rahiman, B. A., Harsha, H. C., Shankar, S., Prasad, T. S. K., Mohan, S. S., Bader, G. D., Wani, M. R. and Pandey, A. (2011). A comprehensive manually curated reaction map of RANKL/RANK signaling pathway. Database (Oxford). 2011, bar021.</Comment>
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    <Comment>RANKL stimulation induces MEK1 phosphorylation in RAW264.7 cells</Comment>
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    <Comment>RANKL stimulation induces MEK1 phosphorylation in RAW264.7 cells</Comment>
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     <Comment>RANKL stimulation induces SYK phosphorylation at Tyr-323 and Tyr-352 in mouse derived bone marrow cells and RAW264.7 cells</Comment>
     <Comment>RANKL stimulation induces SYK phosphorylation at Tyr-323 and Tyr-352 in mouse derived bone marrow cells and RAW264.7 cells</Comment>
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   <DataNode TextLabel="TRAF6" GraphId="ebc51" Type="Protein" GroupRef="de6ac">
     <Comment>TRAF6  undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages. </Comment>
     <Comment>TRAF6  undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages. </Comment>
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   <DataNode TextLabel="TRAF1" GraphId="e2e87" Type="Protein">
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   <DataNode TextLabel="STAT1" GraphId="b86c8" Type="Protein">
   <DataNode TextLabel="STAT1" GraphId="b86c8" Type="Protein">
     <Comment>RANKL stimulation induces STAT1 phosphorylation at Ser-727 in mouse pre-osteoclasts and bone marrow macrophages</Comment>
     <Comment>RANKL stimulation induces STAT1 phosphorylation at Ser-727 in mouse pre-osteoclasts and bone marrow macrophages</Comment>
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   <DataNode TextLabel="IKBKG" GraphId="f7de7" Type="Protein" GroupRef="a8415">
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   <DataNode TextLabel="IKBKB" GraphId="aabcc" Type="Protein" GroupRef="a8415">
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   <DataNode TextLabel="AKT1" GraphId="fc960" Type="Protein" GroupRef="f4b20">
   <DataNode TextLabel="AKT1" GraphId="fc960" Type="Protein" GroupRef="f4b20">
     <Comment>AKT1 undergoes induced phosphorylation upon stimulation with RANKL at Thr-308 and Ser-473 in mouse bone marrow derived macrophages  and in maouse macrophage cell line, RAW264.7.</Comment>
     <Comment>AKT1 undergoes induced phosphorylation upon stimulation with RANKL at Thr-308 and Ser-473 in mouse bone marrow derived macrophages  and in maouse macrophage cell line, RAW264.7.</Comment>
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   <DataNode TextLabel="NFKBIA" GraphId="adaf1" Type="Protein">
   <DataNode TextLabel="NFKBIA" GraphId="adaf1" Type="Protein">
     <Comment>NFKBIA undergoes induced phosphorylation at Ser-32 in mouse bone marrow macrophages and in RAW264.7 cells.</Comment>
     <Comment>NFKBIA undergoes induced phosphorylation at Ser-32 in mouse bone marrow macrophages and in RAW264.7 cells.</Comment>
-
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     <Graphics CenterX="313.3333333333335" CenterY="943.0" Width="50.0" Height="20.0" ZOrder="32881" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="4792"/>
+
     <Xref Database="Entrez Gene" ID="4792" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK9" GraphId="d5368" Type="Protein" GroupRef="ee190">
   <DataNode TextLabel="MAPK9" GraphId="d5368" Type="Protein" GroupRef="ee190">
     <Comment>RANKL induces MAPK9 phosphorylation at Thr-183 and Tyr-185 in mouse bone marrow derived macrophages.</Comment>
     <Comment>RANKL induces MAPK9 phosphorylation at Thr-183 and Tyr-185 in mouse bone marrow derived macrophages.</Comment>
-
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-
     <Xref Database="Entrez Gene" ID="5601"/>
+
     <Xref Database="Entrez Gene" ID="5601" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAP3K7" GraphId="d68bf" Type="Protein" GroupRef="de6ac">
   <DataNode TextLabel="MAP3K7" GraphId="d68bf" Type="Protein" GroupRef="de6ac">
-
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-
     <Xref Database="Entrez Gene" ID="6885"/>
+
     <Xref Database="Entrez Gene" ID="6885" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="PLCG1" GraphId="f2399" Type="Protein">
   <DataNode TextLabel="PLCG1" GraphId="f2399" Type="Protein">
     <Comment>RANKL stimulation induces PLCG1 phosphorylation in bone marrow derived macrophages and RAW264.7 cells.</Comment>
     <Comment>RANKL stimulation induces PLCG1 phosphorylation in bone marrow derived macrophages and RAW264.7 cells.</Comment>
-
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     <Graphics CenterX="70.43881856540082" CenterY="581.5" Width="50.0" Height="20.0" ZOrder="32893" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="5335"/>
+
     <Xref Database="Entrez Gene" ID="5335" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="JUN" GraphId="a9022" Type="Protein" GroupRef="d43d5">
   <DataNode TextLabel="JUN" GraphId="a9022" Type="Protein" GroupRef="d43d5">
     <Comment>JUN undergoes induced phosphorylatin at Ser-63 and Ser-73 in mouse bone marrow derived macrophages, preosteoclasts and 293 cells. Amino acid residues 340-421 of TNFRSF11A are required for its activation</Comment>
     <Comment>JUN undergoes induced phosphorylatin at Ser-63 and Ser-73 in mouse bone marrow derived macrophages, preosteoclasts and 293 cells. Amino acid residues 340-421 of TNFRSF11A are required for its activation</Comment>
-
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-
     <Xref Database="Entrez Gene" ID="3725"/>
+
     <Xref Database="Entrez Gene" ID="3725" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="PTK2" GraphId="dc008" Type="Protein">
   <DataNode TextLabel="PTK2" GraphId="dc008" Type="Protein">
     <Comment>RANKL stimulation induces PTK2 phosphorylation in human umbilical vein endothelial (HUVEC) cells and RAW264.7 cells</Comment>
     <Comment>RANKL stimulation induces PTK2 phosphorylation in human umbilical vein endothelial (HUVEC) cells and RAW264.7 cells</Comment>
-
     <Graphics CenterX="217.25" CenterY="534.5" Width="42.5" Height="20.0" ZOrder="32903" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="217.25" CenterY="534.5" Width="42.5" Height="20.0" ZOrder="32903" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="5747"/>
+
     <Xref Database="Entrez Gene" ID="5747" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="RELA" GraphId="deaa2" Type="Protein" GroupRef="ed6af">
   <DataNode TextLabel="RELA" GraphId="deaa2" Type="Protein" GroupRef="ed6af">
     <Comment>RELA undergoes induced phosphorylation at Ser-276 and Ser-536 upon stimulation with RANKL in mouse bone marrow macrophages. </Comment>
     <Comment>RELA undergoes induced phosphorylation at Ser-276 and Ser-536 upon stimulation with RANKL in mouse bone marrow macrophages. </Comment>
-
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-
     <Xref Database="Entrez Gene" ID="5970"/>
+
     <Xref Database="Entrez Gene" ID="5970" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="AKT2" GraphId="c5f9c" Type="Protein" GroupRef="f4b20">
   <DataNode TextLabel="AKT2" GraphId="c5f9c" Type="Protein" GroupRef="f4b20">
-
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-
     <Xref Database="Entrez Gene" ID="208"/>
+
     <Xref Database="Entrez Gene" ID="208" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK8" GraphId="ec581" Type="Protein" GroupRef="ee190">
   <DataNode TextLabel="MAPK8" GraphId="ec581" Type="Protein" GroupRef="ee190">
     <Comment>RANKL induces MAPK8 phosphorylation at Ser 183 and Tyr-185 in mouse bone marrow macrophages and preosteoclasts</Comment>
     <Comment>RANKL induces MAPK8 phosphorylation at Ser 183 and Tyr-185 in mouse bone marrow macrophages and preosteoclasts</Comment>
-
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-
     <Xref Database="Entrez Gene" ID="5599"/>
+
     <Xref Database="Entrez Gene" ID="5599" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK3" GraphId="cb8bc" Type="Protein" GroupRef="f5f42">
   <DataNode TextLabel="MAPK3" GraphId="cb8bc" Type="Protein" GroupRef="f5f42">
     <Comment>MAPK3 undergoes induced phosphorylation upon stimulation with RANKL at Thr-202 and Tyr-204 in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and dendritic cells.</Comment>
     <Comment>MAPK3 undergoes induced phosphorylation upon stimulation with RANKL at Thr-202 and Tyr-204 in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and dendritic cells.</Comment>
-
     <Graphics CenterX="501.0" CenterY="985.0" Width="58.0" Height="20.0" ZOrder="32919" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="501.0" CenterY="985.0" Width="58.0" Height="20.0" ZOrder="32919" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="5595"/>
+
     <Xref Database="Entrez Gene" ID="5595" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK1" GraphId="e186a" Type="Protein" GroupRef="f5f42">
   <DataNode TextLabel="MAPK1" GraphId="e186a" Type="Protein" GroupRef="f5f42">
     <Comment>MAPK1 undergoes induced phosphorylation upon RANKL stimulation in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and in dendritic cells.</Comment>
     <Comment>MAPK1 undergoes induced phosphorylation upon RANKL stimulation in mouse macrophage cell line, RAW264.7, mouse bone marrow derived macrophages, osteoclasts and in dendritic cells.</Comment>
     <Comment>Type your comment here</Comment>
     <Comment>Type your comment here</Comment>
-
     <Graphics CenterX="501.5" CenterY="1006.0" Width="59.0" Height="20.0" ZOrder="32922" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="501.5" CenterY="1006.0" Width="59.0" Height="20.0" ZOrder="32922" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="5594"/>
+
     <Xref Database="Entrez Gene" ID="5594" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK14" GraphId="d0cf3" Type="Protein">
   <DataNode TextLabel="MAPK14" GraphId="d0cf3" Type="Protein">
     <Comment>MAPK14  undergoes  phosphorylation at Thr-180 and Tyr-182 upon stimulation with RANKL in mouse bone marrow macrophages and pre osteoclasts.</Comment>
     <Comment>MAPK14  undergoes  phosphorylation at Thr-180 and Tyr-182 upon stimulation with RANKL in mouse bone marrow macrophages and pre osteoclasts.</Comment>
-
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     <Graphics CenterX="228.10994397759129" CenterY="982.5588235294122" Width="60.166666666666515" Height="20.0" ZOrder="32927" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="1432"/>
+
     <Xref Database="Entrez Gene" ID="1432" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="CHUK" GraphId="b40d7" Type="Protein" GroupRef="a8415">
   <DataNode TextLabel="CHUK" GraphId="b40d7" Type="Protein" GroupRef="a8415">
     <Comment>CHUK undergoes induced phosphorylation upon stimulation with RANKL in human umbilical vein endothelial cells (HUVECs) and RAW264.7 cells</Comment>
     <Comment>CHUK undergoes induced phosphorylation upon stimulation with RANKL in human umbilical vein endothelial cells (HUVECs) and RAW264.7 cells</Comment>
-
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     <Graphics CenterX="313.8333333333335" CenterY="837.5" Width="50.0" Height="20.0" ZOrder="32946" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="1147"/>
+
     <Xref Database="Entrez Gene" ID="1147" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MTOR" GraphId="a2c7f" Type="Protein">
   <DataNode TextLabel="MTOR" GraphId="a2c7f" Type="Protein">
     <Comment>MTOR undergoes autophosphorylation upon stimulation with RANKL in osteoclasts and RAW264.7 murine macrophage cells.</Comment>
     <Comment>MTOR undergoes autophosphorylation upon stimulation with RANKL in osteoclasts and RAW264.7 murine macrophage cells.</Comment>
-
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     <Graphics CenterX="135.75" CenterY="924.0925589836661" Width="66.5" Height="20.0" ZOrder="32949" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="2475"/>
+
     <Xref Database="Entrez Gene" ID="2475" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="SRC" GraphId="b6d5d" Type="Protein">
   <DataNode TextLabel="SRC" GraphId="b6d5d" Type="Protein">
     <Comment>SRC undergoes induced phosphorylation at tyrosine residue upon stimulation with RANKL in murine bone marrow derived  macrophages, pre-osteoclasts and in RAW264.7 cells.</Comment>
     <Comment>SRC undergoes induced phosphorylation at tyrosine residue upon stimulation with RANKL in murine bone marrow derived  macrophages, pre-osteoclasts and in RAW264.7 cells.</Comment>
-
     <Graphics CenterX="250.0" CenterY="602.0" Width="50.0" Height="20.0" ZOrder="32954" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="250.0" CenterY="602.0" Width="50.0" Height="20.0" ZOrder="32954" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="6714"/>
+
     <Xref Database="Entrez Gene" ID="6714" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TNFSF11" GraphId="ad493" Type="Protein" GroupRef="e099f">
   <DataNode TextLabel="TNFSF11" GraphId="ad493" Type="Protein" GroupRef="e099f">
-
     <Graphics CenterX="234.5" CenterY="316.0" Width="71.0" Height="20.0" ZOrder="32977" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
+
     <Graphics CenterX="234.5" CenterY="316.0" Width="71.0" Height="20.0" ZOrder="32977" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="8600"/>
+
     <Xref Database="Entrez Gene" ID="8600" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TNFSF11" GraphId="b4023" Type="Protein" GroupRef="e099f">
   <DataNode TextLabel="TNFSF11" GraphId="b4023" Type="Protein" GroupRef="e099f">
     <Comment>RANKL self associates to form a homotrimer.</Comment>
     <Comment>RANKL self associates to form a homotrimer.</Comment>
-
     <Graphics CenterX="270.0" CenterY="296.0" Width="62.0" Height="20.0" ZOrder="32979" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="270.0" CenterY="296.0" Width="62.0" Height="20.0" ZOrder="32979" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="8600"/>
+
     <Xref Database="Entrez Gene" ID="8600" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TNFRSF11A" GraphId="dcb34" Type="Protein" GroupRef="e099f">
   <DataNode TextLabel="TNFRSF11A" GraphId="dcb34" Type="Protein" GroupRef="e099f">
-
     <Graphics CenterX="313.0" CenterY="426.0" Width="86.0" Height="20.0" ZOrder="32981" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
+
     <Graphics CenterX="313.0" CenterY="426.0" Width="86.0" Height="20.0" ZOrder="32981" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="8792"/>
+
     <Xref Database="Entrez Gene" ID="8792" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TNFRSF11A" GraphId="b2cd5" Type="Protein" GroupRef="e099f">
   <DataNode TextLabel="TNFRSF11A" GraphId="b2cd5" Type="Protein" GroupRef="e099f">
     <Comment>TNFRSF11A self assembled through its cytoplasmic domain at position 534-539 and formed a trimer in HEK293 cells transfected with TANFRF11A</Comment>
     <Comment>TNFRSF11A self assembled through its cytoplasmic domain at position 534-539 and formed a trimer in HEK293 cells transfected with TANFRF11A</Comment>
-
     <Graphics CenterX="270.0" CenterY="405.0" Width="80.0" Height="20.0" ZOrder="32983" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="270.0" CenterY="405.0" Width="80.0" Height="20.0" ZOrder="32983" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="8792"/>
+
     <Xref Database="Entrez Gene" ID="8792" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TAB2" GraphId="b9e3b" Type="Protein" GroupRef="de6ac">
   <DataNode TextLabel="TAB2" GraphId="b9e3b" Type="Protein" GroupRef="de6ac">
-
     <Graphics CenterX="367.8333333333335" CenterY="687.5" Width="50.0" Height="20.0" ZOrder="33007" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="367.8333333333335" CenterY="687.5" Width="50.0" Height="20.0" ZOrder="33007" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="23118"/>
+
     <Xref Database="Entrez Gene" ID="23118" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="TAB1" GraphId="c8094" Type="Protein" GroupRef="de6ac">
   <DataNode TextLabel="TAB1" GraphId="c8094" Type="Protein" GroupRef="de6ac">
-
     <Graphics CenterX="367.3333333333335" CenterY="707.5" Width="50.0" Height="20.0" ZOrder="33009" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="367.3333333333335" CenterY="707.5" Width="50.0" Height="20.0" ZOrder="33009" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="10454"/>
+
     <Xref Database="Entrez Gene" ID="10454" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="IP3" GraphId="cf196" Type="Metabolite">
   <DataNode TextLabel="IP3" GraphId="cf196" Type="Metabolite">
-
     <Graphics CenterX="70.93881856540082" CenterY="667.5" Width="50.0" Height="20.0" ZOrder="33041" FillColor="ffccff" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" ShapeType="Oval"/>
+
     <Graphics CenterX="70.93881856540082" CenterY="667.5" Width="50.0" Height="20.0" ZOrder="33041" FillColor="ffccff" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" ShapeType="Oval" />
-
     <Xref Database="HMDB" ID="HMDB01498"/>
+
     <Xref Database="HMDB" ID="HMDB0001498" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="NFATC1" GraphId="dd262" Type="Protein">
   <DataNode TextLabel="NFATC1" GraphId="dd262" Type="Protein">
-
     <Graphics CenterX="84.93881856540082" CenterY="1302.021008403363" Width="59.0" Height="20.0" ZOrder="33057" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
+
     <Graphics CenterX="84.93881856540082" CenterY="1302.021008403363" Width="59.0" Height="20.0" ZOrder="33057" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="4772"/>
+
     <Xref Database="Entrez Gene" ID="4772" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="RELA" GraphId="f0e9c" Type="Protein" GroupRef="aa906">
   <DataNode TextLabel="RELA" GraphId="f0e9c" Type="Protein" GroupRef="aa906">
-
     <Graphics CenterX="313.5" CenterY="1248.0" Width="55.0" Height="20.0" ZOrder="33061" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
+
     <Graphics CenterX="313.5" CenterY="1248.0" Width="55.0" Height="20.0" ZOrder="33061" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="5970"/>
+
     <Xref Database="Entrez Gene" ID="5970" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="MAPK14" GraphId="e63c5" Type="Protein">
   <DataNode TextLabel="MAPK14" GraphId="e63c5" Type="Protein">
-
     <Graphics CenterX="228.49369747899186" CenterY="1214.0571857092004" Width="58.5" Height="20.0" ZOrder="33073" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
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     <Graphics CenterX="228.49369747899186" CenterY="1214.0571857092004" Width="58.5" Height="20.0" ZOrder="33073" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="1432"/>
+
     <Xref Database="Entrez Gene" ID="1432" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="CBL" GraphId="cf028" Type="Protein">
   <DataNode TextLabel="CBL" GraphId="cf028" Type="Protein">
     <Comment>RANKL stimulation induced the phosphorylation of CBL at Tyr-731 in mouse macrophage-like cell line, RAW264.7</Comment>
     <Comment>RANKL stimulation induced the phosphorylation of CBL at Tyr-731 in mouse macrophage-like cell line, RAW264.7</Comment>
-
     <Graphics CenterX="250.5" CenterY="655.0" Width="41.0" Height="20.0" ZOrder="33109" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle"/>
+
     <Graphics CenterX="250.5" CenterY="655.0" Width="41.0" Height="20.0" ZOrder="33109" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" />
-
     <Xref Database="Entrez Gene" ID="867"/>
+
     <Xref Database="Entrez Gene" ID="867" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="ROS" GraphId="a2df1" Type="Metabolite">
   <DataNode TextLabel="ROS" GraphId="a2df1" Type="Metabolite">
-
     <Graphics CenterX="182.90336134453787" CenterY="780.4075630252097" Width="50.0" Height="20.0" ZOrder="33129" FillColor="ffccff" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" ShapeType="Oval"/>
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     <Graphics CenterX="182.90336134453787" CenterY="780.4075630252097" Width="50.0" Height="20.0" ZOrder="33129" FillColor="ffccff" FontName="SansSerif" FontWeight="Bold" FontSize="12" Valign="Middle" ShapeType="Oval" />
-
     <Xref Database="ChEBI" ID="CHEBI:26523"/>
+
     <Xref Database="ChEBI" ID="CHEBI:26523" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="CDC42" GraphId="db4d9" Type="Protein" GroupRef="a410b">
   <DataNode TextLabel="CDC42" GraphId="db4d9" Type="Protein" GroupRef="a410b">
-
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     <Xref Database="Entrez Gene" ID="998"/>
+
     <Xref Database="Entrez Gene" ID="998" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="CALCR" GraphId="c48cf" Type="Rna">
   <DataNode TextLabel="CALCR" GraphId="c48cf" Type="Rna">
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     <Xref Database="Entrez Gene" ID="799" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="NFATC1" GraphId="d9b82" Type="Rna">
   <DataNode TextLabel="NFATC1" GraphId="d9b82" Type="Rna">
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     <Xref Database="Entrez Gene" ID="4772"/>
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     <Xref Database="Entrez Gene" ID="4772" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="ACP5" GraphId="d2652" Type="Rna">
   <DataNode TextLabel="ACP5" GraphId="d2652" Type="Rna">
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     <Xref Database="Entrez Gene" ID="54"/>
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     <Xref Database="Entrez Gene" ID="54" />
   </DataNode>
   </DataNode>
   <DataNode TextLabel="SQSTM1" GraphId="fb220" Type="Protein">
   <DataNode TextLabel="SQSTM1" GraphId="fb220" Type="Protein">
     <Comment>TRAF6  undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages.</Comment>
     <Comment>TRAF6  undergoes polyubiquitination upon stimulation with RANKL which is further enhanced by IFN-gamma in mouse macrophage cell line RAW 264.7 and in mouse bone marrow derived macrophages.</Comment>
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   </DataNode>
   <DataNode TextLabel="TNFRSF11A" GraphId="ab90e" Type="Rna">
   <DataNode TextLabel="TNFRSF11A" GraphId="ab90e" Type="Rna">
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   </DataNode>
   <DataNode TextLabel="ICAM1" GraphId="d2f82" Type="Rna">
   <DataNode TextLabel="ICAM1" GraphId="d2f82" Type="Rna">
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   </DataNode>
   <DataNode TextLabel="VCAM1" GraphId="d1845" Type="Rna">
   <DataNode TextLabel="VCAM1" GraphId="d1845" Type="Rna">
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     <Xref Database="Entrez Gene" ID="7412" />
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   </DataNode>
   <DataNode TextLabel="CTSK" GraphId="ced95" Type="Rna">
   <DataNode TextLabel="CTSK" GraphId="ced95" Type="Rna">
     <Comment>Type your comment here</Comment>
     <Comment>Type your comment here</Comment>
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     <Xref Database="Entrez Gene" ID="1513" />
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   </DataNode>
   <DataNode TextLabel="SPI1" GraphId="a1f36" Type="Protein">
   <DataNode TextLabel="SPI1" GraphId="a1f36" Type="Protein">
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   </DataNode>
   <DataNode TextLabel="MAP3K14" GraphId="adf7a" Type="Protein">
   <DataNode TextLabel="MAP3K14" GraphId="adf7a" Type="Protein">
     <Comment>RANKL stimulation leads to the activation of alternative NF-kappa B pathway which induced the formation of p52/RELB heterodimers through the activation of MAP3K14 (NIK). NIK deficient mice impairs RANKL mediated osteoclastogenesis.</Comment>
     <Comment>RANKL stimulation leads to the activation of alternative NF-kappa B pathway which induced the formation of p52/RELB heterodimers through the activation of MAP3K14 (NIK). NIK deficient mice impairs RANKL mediated osteoclastogenesis.</Comment>
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   <DataNode TextLabel="NFKB2" GraphId="fca4e" Type="Protein" GroupRef="f8dc1">
     <Comment>RANKL stimulation induces NFKB2 phosphorylation at Ser-866, Ser-870 in RAW264.7 cells.</Comment>
     <Comment>RANKL stimulation induces NFKB2 phosphorylation at Ser-866, Ser-870 in RAW264.7 cells.</Comment>
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   <DataNode TextLabel="RELB" GraphId="cd3ac" Type="Protein" GroupRef="b603b">
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   <State GraphRef="a6f66" TextLabel="P" GraphId="c74c4">
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     <Comment>Stimulation of RANK receptor with RANKL induces the phosphorylation of GAB2 at Tyr-452 in mouse preosteoclasts.</Comment>
     <Comment>Stimulation of RANK receptor with RANKL induces the phosphorylation of GAB2 at Tyr-452 in mouse preosteoclasts.</Comment>
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     <Comment>TNFSF11 and TNFRSF11A form a heterohexameric complex</Comment>
     <Comment>TNFSF11 and TNFRSF11A form a heterohexameric complex</Comment>
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     <Comment>RANK forms a complex with TRAF6, TAB1, TAB2, and  MAP3K7 upon stimulation with RANKL in 293 cells and leads to the activation of MAP3K7.</Comment>
     <Comment>RANK forms a complex with TRAF6, TAB1, TAB2, and  MAP3K7 upon stimulation with RANKL in 293 cells and leads to the activation of MAP3K7.</Comment>
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     <Comment>MAP2K7 phosphorylates MAPK9 upon stimulation with RANKL  in RAW264.7 cells</Comment>
     <Comment>MAP2K7 phosphorylates MAPK9 upon stimulation with RANKL  in RAW264.7 cells</Comment>
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Line 637: Line 637:
     <Comment>Type your comment here</Comment>
     <Comment>Type your comment here</Comment>
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     <Comment>Activation of AKT by PI3K by TNFRSF11A signaling promotes the survival of osteoclasts through MTOR</Comment>
     <Comment>Activation of AKT by PI3K by TNFRSF11A signaling promotes the survival of osteoclasts through MTOR</Comment>
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     <Comment>Cytoplasmic region of RANK interacts with SRC upon stimulation with RANKL in mouse dendritic cells and human 293T cells.</Comment>
     <Comment>Cytoplasmic region of RANK interacts with SRC upon stimulation with RANKL in mouse dendritic cells and human 293T cells.</Comment>
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     <Comment>AKT is activated by PI3K in a SRC dependent manner in RANKL signaling.</Comment>
     <Comment>AKT is activated by PI3K in a SRC dependent manner in RANKL signaling.</Comment>
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     <Comment>IKBKB phosphorylates NFKBIA upon stimulation with RANKL in RAW264.7 cells</Comment>
     <Comment>IKBKB phosphorylates NFKBIA upon stimulation with RANKL in RAW264.7 cells</Comment>
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     <Comment>Cytoplasmic Ca2+ oscillations occur during TNFRSF11A mediated osteoclastogenesi which leads to the upregulation of NFATC1, a master regulator of osteoclastogenesis.</Comment>
     <Comment>Cytoplasmic Ca2+ oscillations occur during TNFRSF11A mediated osteoclastogenesi which leads to the upregulation of NFATC1, a master regulator of osteoclastogenesis.</Comment>
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     <Comment>NFATC1 translocates from cytoplasm to nucleus upon stimulation with RANKL  in murine bone marrow derived macrophages, osteoclasts and RAW264.7 cells.</Comment>
     <Comment>NFATC1 translocates from cytoplasm to nucleus upon stimulation with RANKL  in murine bone marrow derived macrophages, osteoclasts and RAW264.7 cells.</Comment>
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Line 736: Line 736:
     <Comment>NFKB1 translocated from cytoplasm to nucleus upon stimualtion with RANKL in RAW264.7 cells.</Comment>
     <Comment>NFKB1 translocated from cytoplasm to nucleus upon stimualtion with RANKL in RAW264.7 cells.</Comment>
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     <Comment>MAPK14  translocates  from cytoplasm to nucleus upon stimulation with RANKL in murine bone marrow cells.</Comment>
     <Comment>MAPK14  translocates  from cytoplasm to nucleus upon stimulation with RANKL in murine bone marrow cells.</Comment>
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     <Comment>Interaction of TRAF6 with SRC enhaced the kinase activity of  SRC which in turn leads to the tyrosine phosphorylation of downstream molecule, CBL</Comment>
     <Comment>Interaction of TRAF6 with SRC enhaced the kinase activity of  SRC which in turn leads to the tyrosine phosphorylation of downstream molecule, CBL</Comment>
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     <Comment> LYN inhibits osteclastogenesis by inhibiting the activation of PLCG1 mediated calcium signaling.</Comment>
     <Comment> LYN inhibits osteclastogenesis by inhibiting the activation of PLCG1 mediated calcium signaling.</Comment>
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     <Comment>RANK stimulation leads to the activation of RAC1 in osteoclasts</Comment>
     <Comment>RANK stimulation leads to the activation of RAC1 in osteoclasts</Comment>
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     <Comment>TNFRSF11B (OPG)  is a negative regulator of RANK signaling pathway and inhibits  osteoclastogenesis  in vivo and in vitro</Comment>
     <Comment>TNFRSF11B (OPG)  is a negative regulator of RANK signaling pathway and inhibits  osteoclastogenesis  in vivo and in vitro</Comment>
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     <Comment>UBA domain of TRAF6 interacts with SQSTM1upon stimulation with RANKL in mouse bone marrow derived cells , RAW264.7 cells and in 293 cells. SQSTM1 is an important mediator of RANK- actiavted osteoclastogenesis.</Comment>
     <Comment>UBA domain of TRAF6 interacts with SQSTM1upon stimulation with RANKL in mouse bone marrow derived cells , RAW264.7 cells and in 293 cells. SQSTM1 is an important mediator of RANK- actiavted osteoclastogenesis.</Comment>
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     <Comment>FOS is required for osteoclast differentiation and is an important regulator osteoclast-macrophage lineage determination and bone remodeling in vivo</Comment>
     <Comment>FOS is required for osteoclast differentiation and is an important regulator osteoclast-macrophage lineage determination and bone remodeling in vivo</Comment>
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     <Comment>Inhibitors of MEK's enhanced RANKL-mediated osteoclastogenesis.</Comment>
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+
     <Graphics CenterX="660.1666666666642" CenterY="1076.5567928730597" Width="59.0" Height="19.113585746102444" ZOrder="33825" FillColor="ffccff" FontWeight="Bold" FontSize="12" Valign="Middle" ShapeType="Oval" Rotation="0.0" />
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   <Shape GraphId="cae70">
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     <Graphics CenterX="655.6533496707339" CenterY="554.9288583797635" Width="30.0" Height="31.0" ZOrder="33829" FillColor="ff3399" FontSize="10" Valign="Middle" ShapeType="Oval" Color="ff0066" Rotation="0.0" />
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   <Shape GraphId="e6a91">
   <Shape GraphId="e6a91">
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   <Group GroupId="b603b" GraphId="b9b82" Style="Group" />
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   <Group GroupId="ed6af" GraphId="ab57f" Style="Group"/>
+
   <Group GroupId="e099f" GraphId="ba0ec" Style="Group" />
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   <Group GroupId="a410b" GraphId="be4ce" Style="Group" />
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   <Group GroupId="c192b" GraphId="bfa97" Style="Group"/>
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   <Group GroupId="de6ac" GraphId="c4de6" Style="Group" />
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   <Group GroupId="f4b20" GraphId="cbe75" Style="Group" />
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   <Group GroupId="d43d5" GraphId="dc0a7" Style="Group" />
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+
   <InfoBox CenterX="0.0" CenterY="0.0" />
   <Biopax>
   <Biopax>
     <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
     <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">

Current revision

Error rendering pathway page

This revision of the pathway probably contains invalid GPML code. If this happens to the most recent revision, try reverting the pathway using the pathway history displayed below or contact the site administrators (see WikiPathways:About) to resolve this problem.

Pathway history

View all...
CompareRevisionActionTimeUserComment
106175view12:07, 16 August 2019MaintBotHMDB identifier normalization
90016view19:25, 8 October 2016AlexanderPicoModified description
87426view11:50, 22 July 2016MkutmonModified description
86033view12:21, 28 June 2016EveloModified title
86032view12:20, 28 June 2016EveloModified title
79959view13:10, 28 April 2015Zariannotated IP3 metabolite
79274view21:28, 19 March 2015Zari
78555view10:31, 7 January 2015MaintBotadded missing graphIds
74133view06:04, 1 April 2014EgonwFixed the typing of ROS: the ID is found in the Metabolites mapping file.
74079view14:36, 27 March 2014EgonwGave ROS an ID.
71702view19:53, 17 October 2013MaintBotremoved data source from nodes without identifier
70099view18:45, 12 July 2013MaintBotupdated to 2013 schema
67621view11:34, 26 June 2013DdiglesOntology Term : 'signaling pathway pertinent to development' added !
48442view14:50, 24 May 2012NetPathModified description
45591view09:58, 18 October 2011JyotiModified description
45590view09:57, 18 October 2011JyotiModified description
44630view18:15, 22 September 2011Khanspersupdating content
44130view04:52, 25 August 2011JyotiOntology Term : 'signaling pathway' added !
44080view18:16, 23 August 2011MaintBotAdded category and cleaned up MAPP Info
43947view10:31, 19 August 2011JyotiModified description
43946view10:23, 19 August 2011JyotiNew pathway

Error details

exception 'Exception' with message 'Unable to convert to /var/www/wikipathways/images/b/bf/WP2018_prev.svg:
<BR>Status:1
<BR>Message:Exception in thread "main" java.lang.NullPointerException
	at org.pathvisio.core.Engine.getPathwayImporters(Unknown Source)
	at org.pathvisio.core.Engine.importPathway(Unknown Source)
	at org.pathvisio.core.util.Converter.main(Unknown Source)

<BR>Command:java -Xmx1024M -jar /var/www/wikipathways/wpi/bin/pathvisio_core.jar "/var/www/wikipathways" "/var/www/wikipathways/images/b/bf/WP2018_prev.svg" 2>&1<BR>' in /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php:1255
Stack trace:
#0 /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php(1227): Pathway::convertWithPathVisio(false, '/var/www/wikipa...')
#1 /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php(1137): Pathway->saveConvertedByPathVisioCache('svg')
#2 /var/www/wikipathways/wpi/extensions/Pathways/PathwayPage.php(21): Pathway->updateCache('svg')
#3 [internal function]: renderPathwayPage(Object(Parser), '<?xml version="...', Object(StripState))
#4 /var/www/wikipathways/includes/Hooks.php(125): call_user_func_array('renderPathwayPa...', Array)
#5 /var/www/wikipathways/includes/parser/Parser.php(318): wfRunHooks('ParserBeforeStr...', Array)
#6 /var/www/wikipathways/includes/OutputPage.php(405): Parser->parse('<?xml version="...', Object(Title), Object(ParserOptions), true, true, 106175)
#7 /var/www/wikipathways/includes/OutputPage.php(391): OutputPage->addWikiTextTitle('<?xml version="...', Object(Title), true, true)
#8 /var/www/wikipathways/includes/OutputPage.php(500): OutputPage->addWikiTextTitleTidy('<?xml version="...', Object(Title), true)
#9 /var/www/wikipathways/includes/DifferenceEngine.php(313): OutputPage->addWikiTextTidy('<?xml version="...')
#10 /var/www/wikipathways/includes/DifferenceEngine.php(271): DifferenceEngine->renderNewRevision()
#11 /var/www/wikipathways/includes/Article.php(729): DifferenceEngine->showDiffPage(false)
#12 /var/www/wikipathways/includes/Wiki.php(437): Article->view()
#13 /var/www/wikipathways/includes/Wiki.php(59): MediaWiki->performAction(Object(OutputPage), Object(Article), Object(Title), Object(User), Object(WebRequest))
#14 /var/www/wikipathways/index.php(93): MediaWiki->initialize(Object(Title), Object(Article), Object(OutputPage), Object(User), Object(WebRequest))
#15 {main}
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